The design and construction of synthetic protein mimics

A strate y for the modular construction of synthetic protein mimics base% on the ability of non-protein amino acids to act as stereochemical directors of polypeptide chain folding, is described. The use of d-aminoisobutyric acid (Aib) to construct stereochemically rigid helices is exemplified by crystallographic and spectroscopic studies of several apolar peptides, ranging in len th from seven t o sixteen residues. The problem of linker desfgn i n elaborating a,& motifs is considered. Analysis of protein crystal structure data provides a guide to choosing linking sequences. Attempts at constructing linked helical motifs linking Gly-Pro segments are described. Ths use of f lexii?in!inkers, like € -aminocaproic acid is examined and the crystallographic and solution state analysis of a linked helix motif is presented. The use of bulky sidechain modifications on a helical scaffold, as a means of generatin putative binding sites is exemplified by a crystal structure of a peptide packed in a parallel zipper arrangement.